Table 3.

Sensitivities and Efficacies of Ligand Agonism and Inactivation of Human α4β2-nAChR^a

Compd.	Agonism		Inactivation		Ki (nM)
	EC50 (nM)	Efficacy (%)	IC50 (nM)	Efficacy (%)	α4β2
3	36	13	61	68	0.67±0.20
4	25	13	16	66	0.31±0.10
5	110	20	44	85	0.37±0.10
(−)-Nicotine	290	88	430	93	4.9

^aThe indicated compounds were used in ⁸⁶Rb⁺ efflux assays to define their intrinsic activities as agonists defined by their EC₅₀ values (nM) and efficacies (normalized to that of a full agonist at a maximally efficacious concentration; see Experimental Section, “Agonism”) when acting at human α4β2-nAChRs heterologously and stably expressed in transfected SH-EP1 human epithelial cells. The compounds also were used in efflux assays to define their abilities to inactivate responses to a full agonist at its EC₉₀ concentration as defined by inactivation IC₅₀ values (nM) and inhibitory efficacy (normalized to complete functional inhibition; see Experimental Section, “Inactivation”) when acting at human α4β2-nAChRs. The term “inactivation” is used because compounds may be acting to desensitize receptors and/or as competitive or non-competitive antagonists, and further work is needed to make such a distinction. Also shown for reference are K_i values (nM) for blockade of specific binding of [³H]epibatidine to membrane fractions prepared from (α4β2) HEK cells transfected to express rat α4 and β2 subunits. SEM values were determined for each parameter and although not presented here typically are less than 15% for efficacy measures and no more than a factor of 2 for molar EC₅₀ or IC₅₀ values. Results for compounds 3, 4, and 5 are from 4 independent determinations. Results for nicotine are from Reference 13.